The glutamatergic system plays a role in certain common behavioral manifestations of posttraumatic stress disorder (PTSD), e.g. mechanisms of fear learning and anxious arousal. We propose to evaluate the efficacy of the mGlu2/3 receptor agonist pomaglumetad methionil in treating PTSD in a randomized, double-blind, placebo-controlled, phase II clinical trial. Key endpoints of this trial include structured diagnostic and self- report measures of PTSD and related symptomatology, as well as objective biomarkers of fear acquisition and expression. Evaluation of the differential efficacy of the mGlu2/3 agonist pomaglumetad methionil on symptom clusters that comprise the theory-driven and empirically-supported five-factor phenotypic model of PTSD symptoms will provide greater specificity regarding how this drug differentially modulates unique dimensions of the PTSD phenotype. Given the inhibitory effects of mGlu2/3 receptor agonists on stress-induced NE secretion, we predict that pomaglumetad methionil will have the most pronounced effect in mitigating anxious arousal symptoms.!